Hugs Before Drugs – The Price of Emotional Neglect

Every exhausted parent can be tempted to check out at times, especially when the little ones are testing limits.

A happy child, presumably not neglected, buried in sand. (D. Sharon Pruitt via Wikimedia Commons)

A happy child, presumably not neglected, buried in sand. (D. Sharon Pruitt via Wikimedia Commons)

But when moments of autopilot become months or years, that is considered emotional neglect and it’s strongly linked to the subsequent development of clinical depression in children. Ahmad Hariri’s lab at Duke studies emotional neglect, defined as a caregiver consistently overlooking signs that a child needs comfort or attention, even for something positive.

“Early in life, during infancy, an emotional neglectful parent would regularly be unresponsive and uninvolved with their child,” said Jamie Hanson, a postdoctoral researcher in Hariri’s group. “In early childhood, parents would be clearly unengaged in playing with the child, showing little to no affection during interactions.”

In a study published online in Biological Psychiatry, Hanson, Hariri and their collaborator Douglas Williamson of the University of Texas Health Sciences Center San Antonio, found that the more emotional neglect the children had experienced in their lives, the less responsive their brain was to a reward (winning money in a card game). They had scanned the brains of 106 children between 11 and 15 years of age, and then again two years later.

The scientists focused on the ventral striatum, a brain area known to fire up in response to positive feedback. This region is thought to play a role in optimism and hopefulness, and its dysfunction has been associated with depression. The team wondered: Are the kids with dulled ventral striatum activity more likely to have symptoms of depression? They were.

Ahmad Hariri

Ahmad Hariri

Depression rates start to rise around 15 or 16 years of age, and that’s why the team focused on this age. The cohort of kids they studied were part of Williamson’s Teen Alcohol Outcomes Study (TAOS), and Hanson and Hariri hope to continue following them.

In a different cohort called the Duke Neurogenetics Study, Hariri’s team has found that the responsiveness of the ventral striatum and the amygdala — another area that handles life stress — may help predict how likely young adults are to develop problem drinking in response to stress or to engage in risky sexual behavior.

Being able to identify the children or young adults who are at risk for depression and anxiety is a tall order. But the possibility that we could one day funnel extra support to these individuals and help them avoid a lifetime of medicines and therapy is what keeps Hariri and his team going.

Personally, as a parent, I’m excited see what the Hariri group will do next. During our interview, I couldn’t help running a few scenarios by him and Hanson. Am I emotionally neglecting my toddler if she’s having a tantrum and I have to leave the room or I’ll scream?

“You can have a bad week,” said Hariri, who is also a dad. “You’re not ruining your kid.”

KellyRae_Chi_100Guest post by Kelly Rae Chi, a Cary-based freelance writer who covers brain science for Duke Research.

Pinpointing the Cause of Coughs and Sneezes

Duke students are trying to help doctors find a faster way to pinpoint the cause of their patients’ coughs, sore throats and sniffles.

The goal is to better determine if and when to give antibiotics in order to stem the rise of drug-resistant superbugs, said senior Kelsey Sumner.

For ten weeks this summer, Sumner and fellow Duke student Christopher Hong teamed up with researchers at Duke Medicine to identify blood markers that could be used to tell whether what’s making someone sick is a bacteria, or a virus.

More than half of children who go to the doctor for a sore throat, ear infection, bronchitis or other respiratory illness leave with a prescription for antibiotics, even though the majority of these infections — more than 70% — turn out to be caused by viruses, which antibiotics can’t kill.

The end result is that antibiotics are prescribed roughly twice as often as they should be, to the tune of 11.4 million unnecessary prescriptions a year.

“It’s a big problem,” said Emily Ray Ko, MD, PhD, a physician at Duke Regional Hospital who worked with Sumner and Hong on the project, alongside biostatistician Ashlee Valente and infectious disease researcher Ephraim Tsalik of Duke’s Center for Applied Genomics and Precision Medicine.

Prescribing antibiotics when they aren’t needed can make other infections trickier to treat.

Fast, accurate genetic tests may soon help doctors tell if you really need antibiotics. Photo from the Centers for Disease Control and Prevention.

Fast, accurate genetic tests may soon help doctors tell if you really need antibiotics. Photo from the Centers for Disease Control and Prevention.

That’s because antibiotics wipe out susceptible bacteria, but a few bacteria that are naturally resistant to the drugs survive, which allows them to multiply without other bacteria to keep them in check.

More than two million people develop drug-resistant bacterial infections each year.

A single superbug known as methicillin-resistant Staphylococcus aureus, or MRSA, kills more Americans every year than emphysema, HIV/ AIDS, Parkinson’s disease and homicide combined.

Using antibiotics only when necessary can help, Ko said, but doctors need a quick and easy test that can be performed while the patient is still in the clinic or the emergency room.

“Most doctors need to know within an hour or two whether someone should get antibiotics or not,” Ko said. “Delaying treatment in someone with a bacterial infection could have serious and potentially life threatening consequences, which is one of the main reasons why antibiotics are over-prescribed.”

With help from Sumner and Hong, the team has identified differences in patients’ bloodwork they hope could eventually be detected within a few hours, whereas current tests can take days.

The researchers made use of the fact that bacteria and viruses trigger different responses in the immune system.

They focused on the genetic signature generated by tiny snippets of genetic material called microRNAs, or miRNAs, which play a role in controlling the activity of other genes within the cell.

Using blood samples from 31 people, ten with bacterial pneumonia and 21 with flu virus, they used a technique called RNA sequencing to compare miRNA levels in bacterial versus viral infections.

So far, the researchers have identified several snippets of miRNA that differ between bacterial and viral infections, and could be used to discriminate between the two.

“Hopefully it could be used for a blood test,” Sumner said.

“One goal of these types of assays could be to identify infections before symptoms even appear,” Ko said. “Think early detection of viral infections like Ebola, for example, where it would be helpful to screen people so you know who to quarantine.”

Sumner and Hong were among 40 students selected for a summer research program at Duke called Data+. They presented their work at the Data+ Final Symposium on July 23 in Gross Hall.

Data+ is sponsored by the Information Initiative at Duke, the Social Sciences Research Institute and Bass Connections. Additional funding was provided by the National Science Foundation via a grant to the departments of mathematics and statistical science.

RobinSmith_hed100

 

Writing by Robin Smith; photos and video by Christine Delp and Hannah McCracken

 

 

Brain Camp Makes ‘Aha Moments’

Final presentations for the Neuroscience and Neuroethics Camp were held in the new headquarters of the Duke Institute for Brain Sciences.

Final presentations for the Neuroscience and Neuroethics Camp were held in the new headquarters of the Duke Institute for Brain Sciences. (photo by  Jon Lepofsky)

Given just two weeks to formulate a hypothesis about brains, Duke’s Cognitive Neuroscience and Neuroethics Camp students spoke with impressive confidence as they presented at the Duke Institute for Brain Sciences (DIBS) on July 16.

The high school students had designed experiments using the concepts and methods of cognitive neuroscience to demonstrate what is unique about human brains.

“It was good to see the curiosity, energy, and critical thinking that was present throughout the students’ projects,” said Jon Lepofsky, Academic Director for the Cognitive Neuroscience & Neuroethics camp, the Duke Youth Programs summer program of hands-on, applied problem-solving activities and labs was developed in partnership with DIBS.

Campers dissected sheep brains

The campers dissected real sheep brains

Lepofsky said he was pleased to start the first year of the camp with an engaged, diverse, and thoughtful group of 22 students.

Andie Meddaugh, Xi Yu Liu, Emily Lu and Anand Wong were working on a project involving the logic and the emotion of the human brain. Their hypothesis was that the ability to combine logic and emotion to create a subjective logic shows the difference between human brains and other intelligence processing systems, like artificial intelligence.

Meddaugh said she liked thinking about the brain and logic.

“I enjoy thinking about the problem of what makes us special,” said Meddaugh.

Another group of students presented a project involving the social construct and morality of the brain.

Nicolas Douglass, Abigail Efird, Grace Garret and Danielle Dy are using a hypothesis that suggests if organisms are presented with an issue of resource availability how they respond is a matter of survival.  They proposed using birds, humans, and monkeys to test the reactions of each organism as it is placed outside of its comfort zone.

Abigail Efird said teamwork and “aha moments” were the best way to conduct this project.

“It took human ingenuity and scientific development in order for us to come up with different strategies,” said Efird. “It was surprising to see that humans are not as special and are very much similar to other organisms. “

The group's final "class picture" before heading home to High School.

The group’s final “class picture” before heading home to High School.

Lepofsky said at the end of the program, students will leave with a new set of critical thinking tools and a better understanding of decision- making.

“I know the students will walk away with a deeper understanding of how to evaluate news stories celebrating neuroscience,” Lepofsky said. “They will know how to think like scientists and how to ask quality questions.”

Along with developing a hypothesis on the human brain, the students participated in interactive workshops on perception and other forms of non-conscious processing with Duke researchers. They’ve engaged in debates about topics in neuroethics and neurolaw. In addition to that they went on lab tours and visits to the DiVE.

For more information on Duke’s Cognitive Neuroscience and Neuroethics Camp visit http://www.learnmore.duke.edu/youth/neurosciences/ or call (919) 684-6259.

Warren_Shakira_hed100 Guest post by Shakira Warren, NCCU Summer Intern

Undergrads Share Results, and Lack Thereof

ashby and grundwald

Arts & Sciences Dean Valerie Ashby and Associate Dean for Undergraduate Research Ron Grunwald got the big picture of the poster session from an LSRC landing.

Dozens of Duke undergrads spent the summer working in labs, in part to learn why science is called “research” not “finding.”

“About a third of these students ended up without any data,” said Ron Grunwald, associate dean for undergraduate research, during a Friday poster session in the atrium of the LSRC building for three of the summer research programs.

Biology junior Eric Song gets it now. He spent the summer trying to culture one specific kind of bacteria taken from the abdomens of an ant called Camponotus chromaiodes, which he collected in the Duke Forest. All he got was

Eric Song

Eric Song’s poster featured a photo of the ant and the mysterious white stuff.

“this white stuff showing up and we don’t even know what that is.” His faculty mentor in the Genomics Summer Fellows Program, Jennifer Wernegreen, was hoping to do some genetic sequences on the bacteria, but the 10-week project never made it that far. “We’re only interested in the genome basically,” Song said good-naturedly.

Christine Zhou did get what she set out for, mastering the art of arranging E.coli bacteria in orderly rows of tight little dots, using a specially adapted ink jet printer. Working with graduate student Hannah Meredith and faculty mentor Linchong You, she was able to lay the bugs down at a rate of 500 dots per minute, which might lead to some massive studies. “In the future, we’re hoping to use the different colored cartridges to print multiple kinds of bacteria at the same time,” she said.

Sean Sweat

Sean Sweat (left) discusses her mouse study.

Neuroscience senior Sean Sweat also got good results, finding in her research with faculty mentor Staci Bilbo, that opiate addiction can be lessened in mice by handling them more, and identifying some of the patterns of gene expression that may lie behind that effect.

Neuroscience senior Obia Muoneke wanted to know if adolescents are more likely than children or adults to engage in risky behaviors. Muoneke, who worked with mentor Scott Huettel, said her results showed the influence of peers. “Adolescents are driven to seek rewards while with a peer,” said Muoneke. “Adults are more motivated to avoid losing rewards when they are by themselves.”

The new dean of Trinity College, chemist Valerie Ashby, worked the room asking questions before addressing everyone from a landing overlooking the atrium. “How many of you wake up thinking ‘I want nothing to happen today that I am uncertain about?’” she asked. Well, Ashby continued, scientists need to become comfortable with the unexpected and the unexplainable – such as not having any data after weeks of work.

“We need you to be scientists,” Ashby said, and a liberal arts education is a good start. “If all you took was science classes, you would not be well-educated,” she said.

_ post by Shakira Warren and Karl Leif Bates

Warren_Shakira_hed100

Karl Leif Bates

Is it Just Us?

Plankzooka, on the left there, is two big tubes strapped on either side of the autonomous undersea rover Sentry.

Plankzooka, on the left there, is two big tubes strapped on either side of the autonomous undersea rover Sentry.

We certainly admired the news Friday coming out of a marine science cruise that hasn’t even ended: They found a shipwreck a mile down while also pioneering a new device for gently and precisely sampling plankton at those crushing and dark depths.

But we couldn’t help but notice the “plankzooka’s” uncanny resemblance to a familiar cartoon character.  Here’s an example of some of the juvenile plankton it collected around a methane seep on the sea floor.

plankton

A sampling of juvenile plankton from the deep sea.

 

Middle Schoolers Get a BOOST in Chemistry

Seventy middle school students oohed and aahed as soap bubbles full of propane burst into flame.

“First row, don’t get burned!” shouted Douglass Coleman, director of the BOOST program, a summer science camp program for students in grades 5 through 12.

Duke Chemistry Outreach

Duke Chemistry Outreach student Danielle Holdner makes fire do tricks.

Duke chemistry instructor Ken Lyle and student Danielle Holdner brought their travelling chemistry demos to the MDB Trent Semans Center Monday for the BOOST kids.

They created chemical smoothies and rainbows that taught the students about acids and bases. They sparked up fireworks to teach the students about gases such as butane and propane.

BOOST (Building Opportunities and Overtures in Science and Technology) is designed to teach kids from all cultures and racial backgrounds about science and inspire them to pursue careers in science, technology engineering, medicine and related fields.

“My favorite experiment was the bubbles filled with propane,” said Karen Gonzazlez a student in the program. “I enjoyed seeing them blow up with fire.”

BOOST director Coleman, who is known for his playful antics at the presentations, said the program opens doors for students and provides them with opportunities.

“These kids would not be able to meet with professors or work in labs if it was not for this program,” said Coleman. “It is important that they are around students just like them who are striving and building for success.”

BOOST is divided into three groups depending on grade level and interest of science. Rising 5th and 6th graders are in Boost, rising 7th graders who are interested in food science/chemistry or technology are in Boost XL. Rising 8th graders interested in biological science or engineering are in Boost XXL.

Teachers and junior coaches at the program said it keeps students eager to learn science.

“This program keeps students engaged and motivated in hands- on activities, “said Stefanie Joyner, a teacher for Boost XXL.

Sierra Foster, junior coach for Boost XXL, said BOOST can open students’ eyes to new science.

“This program can build their knowledge and help them understand more than what they might already know,“ said Foster.

BOOST is funded through a grant from the Science Education Partnership Award (SEPA) from the National Institute of Health (NH).

For more information on BOOST, visit http://sites.duke.edu/boost/ or call (919) 681-1045.

Warren_Shakira_hed100Guest Post by Shakira Warren, NC Central University summer intern

Duke’s MOOCs Used to Supplement Education

Startup Stock PhotosA new Duke study of Massive Open Online Courses, or MOOCs, has found that they are democratizing learning by supplementing traditional forms of higher education.

A study of 13 free, open-access digital courses offered by Duke using the Coursera platform illustrates that MOOCs are popular among youngsters, retirees and other non-traditional student populations.

The study is in the current issue of Educational Media International.

Duke researchers analyzed data from pre-course surveys administered to everyone who registered for a Duke MOOC in the Fall 2014 semester. They looked specifically at three groups: people under 18, adults over 65, and people who reported that they did not have access to higher education opportunities. Based on comments from over 9,000 learners who fell into these groups, the researchers found qualitative evidence that MOOCs met their needs for content they would not otherwise have access to.

student_laptop_link“The idea was trying to get a better handle on individuals who were underserved, because so much of the popular press has focused on highly-educated, white (for the most part), upper middle class folks taking Coursera courses,” said Lorrie Schmid, the lead researcher on the study. “We wanted to get a sense of these other groups and how they might be approaching, in similar or different ways, these types of classes. “

The study, based on surveys of MOOC enrollees, found that many people under 18 took MOOCs to learn about topics not taught at their school and to explore different disciplines, often to help them choose their future academic or career path. Adults over 65 often took MOOCs to pursue lifelong learning and keep their minds active, regardless of age, and because they wanted to mentor younger students in their professional field.  In addition, the online courses were the only option for some older adults with limited mobility and finances, the study found.

A few examples: A 10-year-old with autism who is home-schooled reported taking a MOOC to learn more about chemistry. A grandmother took a MOOC course in order to help her granddaughter prepare for nursing school. And a graduate student took a Duke statistics MOOC to hone research and analysis skills.

Schmid said that across all three groups, “the theme that was most pronounced was that Coursera classes were supplementing or enhancing their education that they were getting from other either K-12 or higher education formal courses.”

LockemerGuest Post by Courtney Lockemer, Center for Instructional Technology

Outsmarting HIV With Vaccine Antigens Made to Order

AIDS vaccine researchers may be one step closer to outwitting HIV, thanks to designer antibodies and antigens made to order at Duke.

HIV was identified as the cause of AIDS in 1983. Despite decades of progress in understanding the virus, an effective vaccine remains elusive.

The lack of success is partly due to HIV’s uncanny ability to evade the immune system.

IMG_0674

Duke graduate student Mark Hallen and his advisor, Duke computer science and chemistry professor Bruce Donald. Hallen was awarded a 2015 Liebmann Fellowship for graduate studies.

Now, a team of researchers including Duke computer scientist Bruce Donald and graduate student Mark Hallen have published a 3-D close-up of a designer protein that, if injected into patients, could help the immune system make better antibodies against the virus — a step forward in the 30-year HIV vaccine race.

Led by structural biologist Peter Kwong at the Vaccine Research Center in Bethesda, Maryland, the team’s findings appeared online June 22 in the journal Nature Structural & Molecular Biology.

More than 35 million people worldwide are living with HIV, and about two million more people are infected each year.

Antiretroviral drugs can prevent the virus from reproducing in the body once someone is infected, but only a vaccine can stop it from spreading from one person to the next.

Vaccines work by triggering the immune system to make specialized proteins called antibodies, which prime the body to fight foreign substances. But in the case of HIV, not all antibodies work equally well.

One reason is that HIV is always mutating in the body.

3D print of HIV. Thousands of times smaller than the width of a human hair, the virus is covered with proteins (purple) that enable it to enter and infect human cells. Photo by Daniel Mietchen via Wikimedia Commons.

3D print of HIV. In real life the virus is thousands of times smaller than the width of a human hair. HIV is covered with proteins (purple) that enable it to enter and infect human cells. Photo by Daniel Mietchen via Wikimedia Commons.

HIV incorporates its genetic material into the DNA of its host, hijacking the cell’s replication machinery and forcing it to make more copies of the virus. Each round of replication generates small genetic “mistakes,” resulting in slightly different copies that the host’s antibodies may no longer recognize.

Even before the body makes an antibody that works against one strain, the virus mutates again and makes a new one.

“It’s a race against a moving target,” said Hallen, who was also an undergraduate at Duke majoring in chemistry and mathematics.

In the early 1990s, researchers discovered that a tiny fraction of people infected with HIV are able to produce antibodies that protect against many different strains at once.

These “broadly neutralizing antibodies” fasten to the virus’s surface like a key in a lock and prevent it from invading other cells.

But HIV can evade detection by these powerful antibodies, as the part of its outer coat that is vulnerable to their attack is constantly changing shape.

To overcome this problem, first the researchers needed a close-up look at the region of interest — a spike-shaped virus protein known as Env — in its most vulnerable state.

A 3-D closeup of a key virus protein frozen in a shape the researchers say could serve as a template for a vaccine. Image courtesy of Bruce Donald.

A 3-D closeup of a key virus protein frozen in a shape the researchers say could serve as a template for a vaccine. Image courtesy of Bruce Donald.

With this 3-D blueprint in hand, Hallen and former Duke PhD Ivelin Georgiev developed a scoring system and rated dozens of antibodies according to how well they bound to it. They confirmed that the specific conformation of the Env protein they identified was visible to effective antibodies but not ineffective ones.

The team then identified amino acid sequence changes that would freeze the protein in the desired shape.

Once locked in place, the researchers say, the protein could be injected into patients and used to coax their immune systems into preferentially churning out only the most effective antibodies.

“The idea is to ‘tie’ the protein so that it can’t transition to some other conformation and elicit ineffective antibodies as soon as the effective antibodies bind,” Donald said.

Support for this research included grants from the US National Institutes of Health, the US National Institutes of General Medical Sciences, the US National Institute of Heart, Lung and Blood, the US National Science Foundation and the Bill and Melinda Gates Foundation.

CITATION: “Crystal Structure, Conformational Fixation and Entry-Related Interactions of Mature Ligand-Free HIV-1 Env’,” Kwon, Y. et al. Nature Structural & Molecular Biology, June 22, 2015. DOI: 10.1038/nsmb.3051.

RobinSmith_hed100

 

Robin Smith joined the Office of News and Communications in 2014 after more than ten years as a researcher and writing teacher at Duke. She covers the life and physical sciences across campus.